Association between composite dietary antioxidant index and kidney stone prevalence in adults: data from National Health and Nutrition Examination Survey (NHANES, 2007-2018).

Background: The high prevalence of kidney stones in adults worldwide has prompted research into potential interventions, one of which involves exploring the consumption of antioxidants that may confer protective effects. However, the relationship between the composite dietary antioxidant index (CDAI), a crucial measure used to assess an individual's overall antioxidant capacity from daily dietary intake, and kidney stones remains unclear. Therefore, we conducted cross-sectional analysis to examine the association between CDAI and kidney stone prevalence. Methods: The analysis was conducted utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. Antioxidant intake was derived from two 24-h dietary recalls surveys, while CDAI, a comprehensive measure that includes antioxidants like vitamins A, C, and E, zinc, selenium, and carotenoids, was calculated. Multivariate logistic regression and restricted cubic spline (RCS) regression were utilized to examine the association between CDAI and the prevalence of kidney stones. Results: The study included a total of 28,516 participants, with 2,748 individuals having a history of kidney stones. The median of CDAI was -0.01 (-2.02, 2.37). Individuals in the fourth quartile of CDAI exhibited a significantly lower prevalence of kidney stones compared to those in the first quartile (Odds Ratio [OR] = 0.769 [0.633-0.935]), even after adjusting for potential confounding factors (including age, sex, race, education level, poverty income ratio, smoking status, drinking status, body mass index (BMI), energy intake levels, physical activity level, serum calcium concentration, estimated glomerular filtration rate (eGFR), hypertension, diabetes and supplement use). The RCS analysis revealed a non-linear relationship between CDAI and kidney stone prevalence, with inflection points identified at 0.06 (p for non-linearity = 0.039). Subgroup analysis demonstrated consistent CDAI-kidney stone prevalence associations across all subsets. Furthermore, a significant inverse correlation was observed between CDAI and inflammatory markers. Conclusion: This study provides evidence supporting a reciprocal correlation between adult dietary antioxidant intake, as measured by CDAI, and kidney stone prevalence. These findings emphasize the potential benefits of consuming dietary antioxidants in lowering the risk of kidney stone formation.

Amiloride reduces fructosamine-3-kinase expression to restore sunitinib sensitivity in renal cell carcinoma.

The kidney is a vital organ responsible for water and sodium metabolism, while the primary function of amiloride is to promote the excretion of water and sodium. We investigated amiloride enhanced the sunitinib sensitivity in RCC. We found both sunitinib and amiloride displayed cytotoxicity and exerted the synergy effect in RCC cells in vivo and in vitro arrays. Protein expression profiles were screened via MS/TMT, revealing that FN3K was upregulated in the sunitinib group, and rescued in amiloride and the combination administration. Exogenous FN3K could promote proliferation, invasion and metastasis and decrease the sensitivity of Caki-1 cells to sunitinib, also, exogenous FN3K up-regulated VEGFR2 expression and activated AKT/mTOR signal pathway. More FN3K and VEGFR2 accumulated in R-Caki-1 cells and rescued by amiloride treatment. Co-IP and IF confirmed the interaction between FN3K and VEGFR2. In conclusion, FN3K depletion mediated VEGFR2 disruption promotes amiloride synergized the anti-RCC activity of sunitinib.

Validation of prognostic signature and exploring the immune-related mechanisms for NR3C2 in clear cell renal cell carcinoma.

Background: Previous studies have verified that NR3C2 inhibits tumor cell proliferation, invasion, and migration. However, there is a lack of independent validation cohorts for verifying the prognostic value of NR3C2 in clear cell renal cell carcinoma (ccRCC), and its underlying antitumor mechanisms remain unclear. Methods: We first obtained dates from the online public databases. Then R language or online public database was used for bioinformatics analyses to evaluate the effect of NR3C2 on the diagnosis, prognosis, and immune microenvironment in ccRCC patients. Finally, the results were verified by our own cohort and immunofluorescence (IF) staining. Results: The present study yielded significant findings regarding the expression of NR3C2 in ccRCC compared to control tissues. Specifically, NR3C2 expression was found to be significantly reduced in ccRCC and was observed to be correlated with tumor stage. Additionally, patients with lower NR3C2 expression exhibited shorter overall survival (OS), disease-specific survival, and progress-free survival. Univariable and multivariate Cox analyses further identified NR3C2 expression as an independent prognostic factor for ccRCC. Receiver operating characteristic (ROC) analysis demonstrated that NR3C2 was a highly accurate marker for distinguishing tumors from normal kidney tissue, with an area under the curve (AUC) of 0.959. Further analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that NR3C2 may play a role in various biological processes and pathways related to tumor immune microenvironment (TIM). The expression of NR3C2 exhibited significant positive correlations with the levels of infiltration of CD4+ and CD8+ T cells, as well as an association with immune checkpoints. Conclusions: Our exploratory study suggested that NR3C2 could serve as a novel biomarker for predicting survival in patients with ccRCC and the molecular mechanisms owe partly to immune cell infiltration.

Shared genetic links between bladder cancer and obesity-related traits: A conjunctional false discovery rate study.

Bladder cancer (BCa) is a common cancer worldwide and is often linked with obesity-related comorbidities, but little is known about the underlying genetic mechanisms. To investigate these mechanisms, we used various quantitative tools, including conditional quantile-quantile (Q-Q) plots, conditional false discovery rate (cFDR), and conjunctional conditional false discovery rate (ccFDR), to explore the pleiotropic enrichment of risk loci between BCa and obesity-related traits. We also performed an expression quantitative trait locus (eQTL) analysis to assess the relationship between shared risk loci and gene expression. Finally, we conducted functional annotation using Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analysis. Our findings indicated that there was successive enrichment for a range of obesity-related traits, including body fat percentage, body mass index, fasting insulin, type 2 diabetes mellitus, fasting glucose, high-density lipoprotein cholesterol, total triglycerides, and waist-to-hip ratio. Using the tools mentioned above, we identified 18 significant SNPs and 18 closely related genes (cFDR<0.01) under the condition of 8 obesity-related traits. The SNPs included rs143004880, rs73301337, rs10798572, rs11594929, rs17019138, rs2877, rs149795948, rs142509736, rs12727575, rs1571277, rs12131828, rs635634, rs76895963, rs118081211, rs7044247, rs138895564, rs4135275, and rs148023060. Additionally, we identified 15 novel loci using ccFDR, including rs143004880, rs73301337, rs10798572, rs11594929, rs17019138, rs2877, rs142509736, rs1571277, rs635634, rs76895963, rs12131828, rs118081211, rs7044247, rs138895564, and rs4135275. Of the 2 significant loci that modify gene expression, rs12131828 and rs635634 were identified. The functional annotation indicated that the conditional risk genes mainly participated in the regulation of gene silencing. Our study provided evidence of pleiotropic enrichment between BCa and 8 obesity-related traits, and we identified potential genetic mechanisms underlying this relationship. These findings may help in developing targeted clinical treatments for BCa.

Natural Compounds Derived from Plants on Prevention and Treatment of Renal Cell Carcinoma: A Literature Review.

Renal cell carcinoma (RCC) accounts for roughly 85% of all malignant kidney cancer. Therapeutic options for RCC have expanded rapidly over the past decade. Targeted therapy and immunotherapy have ushered in a new era of the treatment of RCC, which has facilitated the outcomes of RCC. However, the related adverse effects and drug resistance remain an urgent issue. Natural compounds are optional strategies to reduce mobility. Natural compounds are favored by clinicians and researchers due to their good tolerance and low economic burden. Many studies have explored the anti-RCC activity of natural products and revealed relevant mechanisms. In this article, the chemoprevention and therapeutic potential of natural compounds is reviewed and the mechanisms regarding natural compounds are explored.

A 20-Gene Signature Predicting Survival in Patients with Clear Cell Renal Cell Carcinoma Based on Basement Membrane.

Objectives: The most common subtype of renal cell carcinoma, clear cell renal cell carcinoma (ccRCC), has a high heterogeneity and aggressive nature. The basement membrane (BM) is known to play a vital role in tumor metastasis. BM-related genes remain untested in ccRCC, however, in terms of their prognostic significance. Methods: BM-related genes were gleaned from the most recent cutting-edge research. The RNA-seq and clinical data of the ccRCC were obtained from TCGA and GEO databases, respectively. The multigene signature was constructed using the univariate Cox regression and the LASSO regression algorithm. Then, clinical features and prognostic signatures were combined to form a nomogram to predict individual survival probabilities. Using functional enrichment analysis and immune-correlation analysis, we investigated potential enrichment pathways and immunological characteristics associated with BM-related-gene signature. Results: In this study, we built a model of 20 BM-related genes and classified them as high-risk or low-risk, with each having its anticipated risk profile. Patients in the high-risk group showed significantly reduced OS compared with patients in the low-risk group in the TCGA cohort, as was confirmed by the testing dataset. Functional analysis showed that the BM-based model was linked to cell-substrate adhesion and tumor-related signaling pathways. Comparative analysis of immune cell infiltration degrees and immune checkpoints reveals a central role for BM-related genes in controlling the interplay between the immune interaction and the tumor microenvironment of ccRCC. Conclusions: We combined clinical characteristics known to predict the prognosis of ccRCC patients to create a gene signature associated with BM. Our findings may also be useful for forecasting how well immunotherapies would work against ccRCC. Targeting BM may be a therapeutic alternative for ccRCC, but the underlying mechanism still needs further exploration.

Proton-coupled monocarboxylate transporters in cancer: From metabolic crosstalk, immunosuppression and anti-apoptosis to clinical applications.

The Warburg effect is known as the hyperactive glycolysis that provides the energy needed for rapid growth and proliferation in most tumor cells even under the condition of sufficient oxygen. This metabolic pattern can lead to a large accumulation of lactic acid and intracellular acidification, which can affect the growth of tumor cells and lead to cell death. Proton-coupled monocarboxylate transporters (MCTs) belong to the SLC16A gene family, which consists of 14 members. MCT1-4 promotes the passive transport of monocarboxylate (e.g., lactate, pyruvate, and ketone bodies) and proton transport across membranes. MCT1-4-mediated lactate shuttling between glycolytic tumor cells or cancer-associated fibroblasts and oxidative tumor cells plays an important role in the metabolic reprogramming of energy, lipids, and amino acids and maintains the survival of tumor cells. In addition, MCT-mediated lactate signaling can promote tumor angiogenesis, immune suppression and multidrug resistance, migration and metastasis, and ferroptosis resistance and autophagy, which is conducive to the development of tumor cells and avoid death. Although there are certain challenges, the study of targeted drugs against these transporters shows great promise and may form new anticancer treatment options.

Kidney microbiota dysbiosis contributes to the development of hypertension.

Gut microbiota dysbiosis promotes metabolic syndromes (e.g., hypertension); however, the patterns that drive hypertensive pathology and could be targeted for therapeutic intervention are unclear. We hypothesized that gut microbes might translocate to the kidney to trigger hypertension. We aimed to uncover their method of colonization, and thereby how to maintain blood pressure homeostasis. Using combined approaches based on fluorescence in situ hybridization (FISH) and immunofluorescence staining, electron microscopy analysis, bacterial cultures, species identification, and RNA-sequencing-based meta-transcriptomics, we first demonstrated the presence of bacteria within the kidney of spontaneously hypertensive rats (SHRs) and its normotensive counterpart, Wistar-Kyoto rats (WKYs), and patients with hypertension. Translocated renal bacteria were coated with secretory IgA (sIgA) or remained dormant in the L-form. Klebsiella pneumoniae (K.pn) was identified in the kidneys of germ-free (GF) mice following intestinal transplantation, which suggested an influx of gut bacteria into the kidneys. Renal bacterial taxa and their function are associated with hypertension. Hypertensive hosts showed increased richness in the pathobionts of their kidneys, which were partly derived from the gastrointestinal tract. We also demonstrated the indispensable role of bacterial IgA proteases in the translocation of live microbes. Furthermore, Tartary buckwheat dietary intervention reduced blood pressure and modulated the core renal flora-host ecosystem to near-normal states. Taken together, the unique patterns of viable and dormant bacteria in the kidney provide insight into the pathogenesis of non-communicable chronic diseases and cardiometabolic diseases (e.g., hypertension), and may lead to potential novel microbiota-targeted dietary therapies.

CDCA3 Predicts Poor Prognosis and Affects CD8+ T Cell Infiltration in Renal Cell Carcinoma.

Background: Cell division cycle associated 3 (CDCA3) mediates the ubiquitination WEE1 kinase at G2/M phase. However, its contribution to cancer immunity remains uncertain. Methods: We first evaluated the effect of CDCA3 on the prognosis of patients with renal cell carcinoma (RCC). The results of bioinformatics analysis were verified by the tissue microarray, immunofluorescence (IF) staining, CCK-8 assay, colony formation, cell cycle, and Western blot. Results: Bioinformatics analysis predicated CDCA3 was an independent predictor of poor prognosis in RCC and was associated with poor TNM stage and grade. CDCA3 was related to the infiltration of CD8+ T cells and Tregs. Tissue microarray demonstrated that CDCA3 was strongly associated with poor prognosis and positively relevant to CD8+ T infiltration. In vitro experiments showed that exgenomic interference of CDCA3 could attenuate cellular proliferation, arrest cell cycle, and blockade accumulation of CDK4, Bub3, and Cdc20 in mitosis process. Conclusion: CDCA3 presents as a good biomarker candidate to predict the prognosis of RCC patients and potentiates the immune tumor microenvironment (TME) of RCC.

Delayed ileal neobladder fistula caused by bladder stones: a case report.

BACKGROUND: Ileal neobladder fistula is a rare complication after radical cystectomy, with an incidence of approximately 0.7%. At present, there are scattered reports of vesicoileal fistula, but there are no reports of ileal neobladder fistula (INF) caused by bladder stones. In this paper, a case of ileal neobladder fistula caused by chronic stimulation of bladder stones was successfully diagnosed and treated. CASE PRESENTATION: A 68-year-old man who had undergone radical cystectomy and an orthotopic ileal neobladder procedure 10 years prior presented with refractory diarrhoea and oliguria and was diagnosed with ileal neobladder fistula caused by chronic stimulation of bladder stones. We performed fistulectomy, cystotomy, partial ileectomy, and end-to-end ileal anastomosis, and the patient recovered and was discharged after the operation. CONCLUSION: Urinary calculi are delayed complications of orthotopic neobladder construction after total cystectomy. Bladder stones are a rare complication of ileal neovesical fistula, which can cause neovesical cutaneous fistula. It is difficult to diagnose through routine examination and easily misdiagnosed as acute gastroenteritis. Surgery is an effective treatment for INF and can achieve a good prognosis.

MiR-125b promotes migration and invasion by targeting the vitamin D receptor in renal cell carcinoma.

Purpose: To investigate the expression of miR-125b and vitamin D receptor (VDR) in renal cell carcinoma (RCC) and assess the biological function of miR-125b in RCC. Methods: We used quantitative real-time polymerase chain reaction (RT-PCR) to detect the expression of nucleic acids and western blotting to analyze the protein abundance in RCC cell lines. MiR-125b mimic and inhibitor were employed to investigate the function and behavior of miR-125b in RCC cell lines. The relationship between miR-125 and VDR was verified using luciferase assays. Results: Overexpression of miR-125b promoted migration and invasion and prevent cell apoptosis in ACHN cells. In contrast, miR-125b deficiency suppressed migration and invasion and induced cell apoptosis in 786-O cells. Luciferase assays indicated the interaction between miR-125b and VDR. In collected samples, miR-125b was significantly higher in RCC tissues and negatively correlated to VDR (r=-0.444, p=0.04). Conclusion: MiR-125b displays an oncogene profile in RCC, patients with high expression of miR-125b should be a more frequent follow-up. MiR-125B may be a potential therapeutic target for RCC.

Differential expression of epithelial sodium channels in human RCC associated with the prognosis and tumor stage: Evidence from integrate analysis.

Background: Epithelial sodium channels are disputed in renal cell carcinoma, but its functions and effects on clinical outcomes are not well understood. Materials and Methods: IHC and PT-PCR were used to detect ENaCα, ß, γ, AVPR2, AQP2, and MR expression in the primary tumor and peritumoral tissues. GEPIA online tool was used to analyze the relationship between epithelial sodium channels and clinical-pathological characteristics. Tumor IMmune Estimation Resource online tool was used to investigate the immune profile relevant to epithelial sodium channels expression. Results: Quantitative RT-PCR analysis revealed that ENaCα, ß, γ, AQP2, and AVPR2 mRNA were decreased in the RCC, but there was no difference in MR mRNA expression between kidney and RCC (p=0.238). The IHC analyses showed that the intensely positive staining of ENaCα, ß, γ, AVPR2, and AQP in the renal tubular and the attenuated in the RCCs. MR displayed moderate staining in both RCC and normal tissue. With the promotion of staging, the expression of AQP2, AVPR2, and MR reduced gradually and predicted a better prognosis. Although ENaCα, ß, and γ were unable to associate with staging, we still observed a high expression of ENaCß and γ displayed a poorer prognosis of RCC. Conclusions: ENaCs shows an oncogene profile in RCC, drugs targeting epithelial sodium channel should be a possible therapeutic way to treat RCC. AVPR2 and MR exhibit an encouraging immunomodulatory function; patients with low expression of AVPR2 and MR may obtain more benefit from immunotherapy.

Metformin reverses the drug resistance of cisplatin in irradiated CNE-1 human nasopharyngeal carcinoma cells through PECAM-1 mediated MRPs down-regulation.

Objective: To explore a way to reverse the drug resistance for irradiated CNE-1 human nasopharyngeal carcinoma cells and try to develop a new high efficacy with low toxicity therapeutic approach. Methods: 300 Gy irradiated the CNE-1 human nasopharyngeal carcinoma cells, and then treated with single-agent cisplatin or metformin, or combination of both drugs. MTT assay and FCM were applied to detect cell viability and apoptosis. Western blot and RT-PCR were used to characterize the protein and mRNA expression after various drug administrations. Results: The results presented single-agent metformin was capable of arresting the tumor growth and inducing apoptosis in irradiated CNE-1 cells and also demonstrated a synergy effect with cisplatin. Furthermore, metformin down-regulates the PECAM-1 expression, which could regulate Multi-drug Resistance-associate Proteins (MRPs) expression leading to cisplatin resistance of irradiated CNE-1 cells. A pan-MRP inhibitor, probenecid, can resecure cisplatin resistance leading by radiation. Conclusions: Metformin, due to its independent effects on PECAM-1, had a unique anti-proliferative effect on irradiated CNE-1 cells. It would be a new therapeutic option to conquer cisplatin resistance for advanced NPC patients after radiotherapy.

CSTP1 inhibits IL-6 expression through targeting Akt/FoxO3a signaling pathway in bladder cancer cells.

CSTP1, a recently identified protein phosphotase, is frequently repressed in bladder cancers. Previous results showed that CSTP1 over-expression inhibited cell cycle progression and promoted apoptosis through dephosphorylating Akt kinase at Ser473 site in bladder cancer cells, but the mechanisms how CSTP1 exerted tumor suppressive activity remains unclear. In this study, we analyzed the gene expression profile changes that affected by CSTP1 overexpression by microarray, and reported that CSTP1 decreased IL-6 expression/secretion in bladder cancer cells and re-expression of IL-6 abrogated CSTP1's tumor suppressive activity. We also found that FoxO3a occupy IL-6 gene promoter and repressed IL mRNA transcription. Further results showed that decreased expression of IL-6 in CSTP1-overexpressing cells inactivated Stat3 transcriptional factor, which resulted in the down-regulation of cyclin D1, Bcl-xl expression. Spearman correlation analysis revealed that the mRNA level of CSTP1 correlated inversely with that of IL-6 in bladder cancer tissues. In conclusion, our studies revealed that protein phosphotase CSTP1 inhibited IL-6 expression through targeting Akt/FoxO3a signaling pathway and IL-6 inactivated Stat3 was necessary for CSTP1's tumor suppressive function.

Decreased expression of TRPV1 in renal cell carcinoma: association with tumor Fuhrman grades and histopathological subtypes.

PURPOSE: The aim of this study was to investigate whether the expression of the ligand-gated Ca2+ channel transient receptor potential vanilloid type-1 (TRPV1) in primary human renal cell carcinoma (RCC) is associated with clinicopathological features. PATIENTS AND METHODS: Fresh and frozen primary tumor and normal peritumoral kidney tissues from 127 patients diagnosed with RCC were analyzed for TRPV1 expression by quantitative reverse transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry. RESULTS: Quantitative RT-PCR revealed that TRPV1 was decreased 3.20-fold in RCC tissue vs normal peritumoral kidney tissue (p=0.012). Significantly different TRPV1 mRNA expression was detected in RCC tissues of different Fuhrman grades and histopathological subtypes (F=4.282, p=0.015 and F=5.205, p=0.014, respectively). Decreased TRPV1 expression was correlated with RCC histopathological subtype (R=-0.554, p=0.003) and Fuhrman grade (R=-0.525, p=0.006). Western blot analysis of TRPV1 protein expression showed similar results. Immunohistochemical analysis showed strong expression of TRPV1 in kidney tubules but demonstrated weak or no immunostaining in RCC tissues. CONCLUSION: TRPV1 expression was decreased in RCC, which was significantly associated with tumor Fuhrman grades and histopathological subtypes. It seems to suggest that TRPV1 expression may be a valuable tool to predict the extent of RCC progression.

Vitamin D receptor suppresses proliferation and metastasis in renal cell carcinoma cell lines via regulating the expression of the epithelial Ca2+ channel TRPV5.

We previously demonstrated that transient receptor potential vanilloid subfamily 5 (TRPV5) expression was decreased in renal cell carcinoma (RCC) compared with that in normal kidney tissues, a finding that was correlated with vitamin D receptor (VDR) expression, but further investigations is warranted. The aim of this study was to elucidate whether VDR could regulate the expression of TRPV5 and affect proliferation and metastasis in RCC. In this study, we used lentivirus to conduct the model of VDR overexpression and knockdown caki-1 and 786-O RCC cell lines in vitro. The results demonstrated that VDR overexpression significantly inhibited RCC cells proliferation, migration and invasion, and promoted apoptosis by the MTT, transwell cell migration/invasion and flow cytometry assays, respectively. However, VDR knockdown in RCC cells had the opposite effect. The RNA-sequence assay, which was assessed in caki-1 cells after VDR overexpression and knockdown, also indicated that significantly differentially expressed genes were associated with cell apoptotic, differentiation, proliferation and migration. RT-PCR and western blot analysis showed that VDR knockdown increased TRPV5 expression and VDR overexpression decreased TRPV5 expression in caki-1 cells. Furthermore, knockdown of TRPV5 expression suppressed the VDR knockdown-induced change in the proliferation, migration and invasion in caki-1 cells. Taken together, these findings confirmed that VDR functions as a tumour suppressor in RCC cells and suppresses the proliferation, migration and invasion of RCC through regulating the expression of TRPV5.

Decreased expression of the epithelial Ca2+ channel TRPV5 and TRPV6 in human renal cell carcinoma associated with vitamin D receptor.

PURPOSE: We investigated the expression of epithelial Ca(2+) channel TRPV (transient receptor potential vanilloid subfamily) 5 and 6, and vitamin D receptor in primary human renal cell carcinoma and benign peritumor tissues, and assessed the possible association between TRPV5/6 and vitamin D receptor expression. MATERIALS AND METHODS: Fresh-frozen primary tumor and peritumor tissues from 27 patients diagnosed with renal cell carcinoma were analyzed for TRPV5/6 and vitamin D receptor expression by quantitative reverse transcriptase-polymerase chain reaction, Western blot and immunohistochemistry. RESULTS: Quantitative reverse transcriptase-polymerase chain reaction revealed that TRPV5/6 and vitamin D receptor expression was decreased 38.11, 4.44 and 3.20 times in renal cell carcinoma vs normal kidney tissue (p = 0.012, 0.002 and 0.020, respectively). Relatively higher expression was noted for chromophobe renal cell carcinoma than for the other renal cell carcinoma subtypes. Vitamin D receptor mRNA expression significantly correlated with that of TRPV6 (r = 0.508, p = 0.007) and TRPV5 (r = 0.697, p = 0.032) in renal cell carcinoma. Western blot showed results similar to those of reverse transcriptase-polymerase chain reaction. Different expression was detected between kidney and renal cell carcinoma tissue. Immunohistochemical analysis verified strong detection of TRPV5/6 and vitamin D receptor in distal nephrons but demonstrated weak or no immunostaining much more often in renal cell carcinoma. CONCLUSIONS: Decreased TRPV5/V6 expression was noted in renal cell carcinoma, which correlated with vitamin D receptor. Different expression was also detected among the different renal cell carcinoma histopathological subtypes. Our observations suggest that altered vitamin D receptor expression may be associated with renal cell carcinoma carcinogenesis via TRPV5/6.

Transvaginal sonographic diagnosis of female urethral diverticula.

PURPOSE: We report our experience with transvaginal sonography (TVUS) in the diagnosis of female urethral diverticulum (UD). METHOD: We reviewed the TVUS examinations of 4 patients with a clinical diagnosis of UD and correlated the sonographic findings with the operative findings, especially regarding the UD's size, content, and location. RESULTS: All UDs were demonstrated on TVUS. The size, content, and location of the UD correlated well with the operative findings. CONCLUSION: TVUS is accurate in diagnosis and determination of the size, content, and location of female UD.

Overexpression of JKTBP1 induces androgen-independent LNCaP cell proliferation through activation of epidermal growth factor-receptor (EGF-R).

Heterogenous nuclear ribonucleoprotein D-like protein (JKTBP) belongs to a new member of hnRNPs. Previous studies implied that JKTBP1 may be associated with the progression of androgen-independent (AI) prostate cancer. In this study, we generated three stable LNCaP cell lines which expressed exogenous JKTBP1. Furthermore, the effect of ectopic JKTBP1 on the proliferation of LNCaP cells and its mechanism was investigated. We originally found that the ectopic JKTBP1 expression resulted in the proliferation of LNCaP cells in an AI way, as well as inducing the upregulated expression of EGF-R and prostate-specific antigen (PSA), but did not influence the expression level of AR. Moreover, AG1478 suppressed the effect of proliferation induced by JKTBP1. In addition, immunohistochemistry showed that JKTBP1 expression was significantly elevated in AI prostate cancer tissues when compared with the androgen-dependent (AD) prostate cancer and benign prostatic hyperplasia. Our data indicated that overexpression of JKTBP1 in LNCaP cells leads to abnormal cell proliferation and may be involved in the process of AD to AI through induction of EGF-R expression.

Comparative proteomics and correlated signaling network of rat hippocampus in the pilocarpine model of temporal lobe epilepsy.

In temporal lobe epilepsy (TLE), the seizure origin typically involves the hippocampal formation. The pilocarpine-induced TLE provides a model to investigate the molecular and functional characterization of epileptogenesis by mimicking the human epileptic condition. Here, we employed a 2-D gel-based proteomic technique to profile proteome changes in the rat hippocampus after pilocarpine treatment. Using MALDI MS and MS/MS, 57 differentially expressed proteins were identified, which were found either up-regulated and/or down-regulated at the two time points 12 h (acute period; Ap) and 72 h (silent period; Sp) compared with the control. These proteins can be related to underlying mechanism of pilocarpine-induced TLE, indicating cytoskeleton modification, altered synaptic function, mitochondrial dysfunction, changed ion channel, and chaperone. Five of the identified proteins, synaptosomal-associated protein 25 (SNAP25), synapsin-2 (SYN2), homer protein homolog 2 (HOMER2), alpha-internexin (INA), and voltage-dependent anion channel 2 (VDAC2) were investigated by semiquantitative RT-PCR, and SNAP25 and INA were further validated by Western blot and immunohistochemistry staining. Furthermore, association of these pilocarpine-induced proteins with biological functions using the Ingenuity Pathway Analysis (IPA) tool showed that nucleic acid metabolism, system development, tissue and cell morphology were significantly altered. IPA of the canonical networks indicated that six membrane proteins (e.g., SNAP25, SYN2, and HOMER2) participated in three biological networks as starting proteins. Our results offer a clue to identify biomarkers for the development of pharmacological therapies targeted at epilepsy.